Prediction of Treatment Efficacy and Telaprevir-Resistant Variants after Triple Therapy in Patients Infected with HCV Genotype 1

J Clin Microbiol. 2013 Jun 19. [Epub ahead of print]

Akuta N, Suzuki F, Fukushima T, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Hara T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H.

Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan.

Abstract

It is often difficult to predict the response to telaprevir/peginterferon (PEG-IFN)/ribavirin therapy and appearance of telaprevir-resistant variants. The present study determined the predictive factors of sustained virological response (SVR) to 12- or 24-week triple therapy (T12PR12 or T12PR24) in 194 Japanese patients infected with hepatitis C virus (HCV) genotype 1b. The study also evaluated whether ultra-deep sequencing technology can predict the emergence of resistant variants at baseline. Analysis of data of the entire group indicated that SVR was achieved by 78% of the patients. Multivariate analysis identified IL28B rs8099917 (genotype TT), substitution of aa70 (Arg70), response to prior treatment (naive or relapse), PEG-IFN dose (≥1.3 μg/kg), and treatment regimen (T12PR24) as significant determinants of SVR. Among patients of the T12PR24 group, 92% with genotype TT achieved SVR, irrespective of substitution of aa70. In patients with genotype non-TT, SVR was 76% for those of Arg70; while only 14% of patients with genotype non-TT, Gln70(His70) and non-response to ribavirin combination therapy achieved SVR. Ultra-deep sequencing was conducted in 17 patients who did not achieve SVR to determine the emergence of resistant variants during therapy. De novo resistant variants were detected in 16 of 17 patients (94%), regardless of variants frequencies at baseline. In conclusion, the results indicated that the response to triple therapy could be predicted by the combination of host, viral, and treatment factors, and that it is difficult to predict at baseline the emergence of telaprevir-resistant variants during triple therapy, even with the use of ultra-deep sequencing.

PMID: 23784126 [PubMed - as supplied by publisher]

Source